LOCUS       NM_005599               2512 bp    mRNA    linear   PRI 03-APR-2024
DEFINITION  Homo sapiens nescient helix-loop-helix 2 (NHLH2), transcript
            variant 1, mRNA.
ACCESSION   NM_005599
VERSION     NM_005599.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2512)
  AUTHORS   Madsen,A.T. and Good,D.J.
  TITLE     In Silico Examination of Single Nucleotide Missense Mutations in
            NHLH2, a Gene Linked to Infertility and Obesity
  JOURNAL   Int J Mol Sci 24 (4), 3193 (2023)
   PUBMED   36834605
  REMARK    GeneRIF: In Silico Examination of Single Nucleotide Missense
            Mutations in NHLH2, a Gene Linked to Infertility and Obesity.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2512)
  AUTHORS   Topaloglu,A.K., Simsek,E., Kocher,M.A., Mammadova,J., Bober,E.,
            Kotan,L.D., Turan,I., Celiloglu,C., Gurbuz,F., Yuksel,B. and
            Good,D.J.
  TITLE     Inactivating NHLH2 variants cause idiopathic hypogonadotropic
            hypogonadism and obesity in humans
  JOURNAL   Hum Genet 141 (2), 295-304 (2022)
   PUBMED   35066646
  REMARK    GeneRIF: Inactivating NHLH2 variants cause idiopathic
            hypogonadotropic hypogonadism and obesity in humans.
REFERENCE   3  (bases 1 to 2512)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   4  (bases 1 to 2512)
  AUTHORS   Afshar,H., Adelirad,F., Kowsari,A., Kalhor,N., Delbari,A.,
            Najafipour,R., Foroughan,M., Bozorgmehr,A., Khamse,S.,
            Nazaripanah,N. and Ohadi,M.
  TITLE     Natural Selection at the NHLH2 Core Promoter Exceptionally Long
            CA-Repeat in Human and Disease-Only Genotypes in Late-Onset
            Neurocognitive Disorder
  JOURNAL   Gerontology 66 (5), 514-522 (2020)
   PUBMED   32877896
  REMARK    GeneRIF: Natural Selection at the NHLH2 Core Promoter Exceptionally
            Long CA-Repeat in Human and Disease-Only Genotypes in Late-Onset
            Neurocognitive Disorder.
REFERENCE   5  (bases 1 to 2512)
  AUTHORS   Yin,Y., Morgunova,E., Jolma,A., Kaasinen,E., Sahu,B.,
            Khund-Sayeed,S., Das,P.K., Kivioja,T., Dave,K., Zhong,F.,
            Nitta,K.R., Taipale,M., Popov,A., Ginno,P.A., Domcke,S., Yan,J.,
            Schubeler,D., Vinson,C. and Taipale,J.
  TITLE     Impact of cytosine methylation on DNA binding specificities of
            human transcription factors
  JOURNAL   Science 356 (6337) (2017)
   PUBMED   28473536
REFERENCE   6  (bases 1 to 2512)
  AUTHORS   Good,D.J., Coyle,C.A. and Fox,D.L.
  TITLE     Nhlh2: a basic helix-loop-helix transcription factor controlling
            physical activity
  JOURNAL   Exerc Sport Sci Rev 36 (4), 187-192 (2008)
   PUBMED   18815487
  REMARK    GeneRIF: proposes the novel hypothesis that transcriptional
            activity by Nhlh2 (NHLH2 in humans) controls either the ability or
            the motivation for exercise [review]
            Review article
REFERENCE   7  (bases 1 to 2512)
  AUTHORS   Han,C., Liu,H., Liu,J., Yin,K., Xie,Y., Shen,X., Wang,Y., Yuan,J.,
            Qiang,B., Liu,Y.J. and Peng,X.
  TITLE     Human Bex2 interacts with LMO2 and regulates the transcriptional
            activity of a novel DNA-binding complex
  JOURNAL   Nucleic Acids Res 33 (20), 6555-6565 (2005)
   PUBMED   16314316
  REMARK    Publication Status: Online-Only
REFERENCE   8  (bases 1 to 2512)
  AUTHORS   Aoyama,M., Ozaki,T., Inuzuka,H., Tomotsune,D., Hirato,J.,
            Okamoto,Y., Tokita,H., Ohira,M. and Nakagawara,A.
  TITLE     LMO3 interacts with neuronal transcription factor, HEN2, and acts
            as an oncogene in neuroblastoma
  JOURNAL   Cancer Res 65 (11), 4587-4597 (2005)
   PUBMED   15930276
  REMARK    GeneRIF: The deregulated expression of neuronal-specific LMO3 and
            HEN2 contributes to the genesis and progression of human
            neuroblastoma in a lineage-specific manner.
REFERENCE   9  (bases 1 to 2512)
  AUTHORS   Lipkowitz,S., Gobel,V., Varterasian,M.L., Nakahara,K., Tchorz,K.
            and Kirsch,I.R.
  TITLE     A comparative structural characterization of the human NSCL-1 and
            NSCL-2 genes. Two basic helix-loop-helix genes expressed in the
            developing nervous system
  JOURNAL   J Biol Chem 267 (29), 21065-21071 (1992)
   PUBMED   1328219
REFERENCE   10 (bases 1 to 2512)
  AUTHORS   Brown,L., Espinosa,R. 3rd, Le Beau,M.M., Siciliano,M.J. and Baer,R.
  TITLE     HEN1 and HEN2: a subgroup of basic helix-loop-helix genes that are
            coexpressed in a human neuroblastoma
  JOURNAL   Proc Natl Acad Sci U S A 89 (18), 8492-8496 (1992)
   PUBMED   1528853
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            DA608185.1, BC096360.1 and AL449264.18.
            
            On Dec 1, 2007 this sequence version replaced NM_005599.2.
            
            Transcript Variant: This variant (1) represents the longer
            transcript.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data because no single transcript was available
            for the full length of the gene. The extent of this transcript is
            supported by transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: M96740.1, SRR1660809.6404.1
                                           [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000320238.3/ ENSP00000322087.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-54                DA608185.1         1-54
            55-1102             BC096360.1         1-1048
            1103-2512           AL449264.18        102904-104313       c
FEATURES             Location/Qualifiers
     source          1..2512
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p13.1"
     gene            1..2512
                     /gene="NHLH2"
                     /gene_synonym="bHLHa34; HEN2; HH27; NSCL2"
                     /note="nescient helix-loop-helix 2"
                     /db_xref="GeneID:4808"
                     /db_xref="HGNC:HGNC:7818"
                     /db_xref="MIM:162361"
     exon            1..179
                     /gene="NHLH2"
                     /gene_synonym="bHLHa34; HEN2; HH27; NSCL2"
                     /inference="alignment:Splign:2.1.0"
     exon            180..508
                     /gene="NHLH2"
                     /gene_synonym="bHLHa34; HEN2; HH27; NSCL2"
                     /inference="alignment:Splign:2.1.0"
     exon            509..2512
                     /gene="NHLH2"
                     /gene_synonym="bHLHa34; HEN2; HH27; NSCL2"
                     /inference="alignment:Splign:2.1.0"
     CDS             517..924
                     /gene="NHLH2"
                     /gene_synonym="bHLHa34; HEN2; HH27; NSCL2"
                     /note="HEN-2; NSCL-2; class A basic helix-loop-helix
                     protein 34"
                     /codon_start=1
                     /product="helix-loop-helix protein 2"
                     /protein_id="NP_005590.1"
                     /db_xref="CCDS:CCDS885.1"
                     /db_xref="GeneID:4808"
                     /db_xref="HGNC:HGNC:7818"
                     /db_xref="MIM:162361"
                     /translation="MMLSPDQAADSDHPSSAHSDPESLGGTDTKVLGSVSDLEPVEEA
                     EGDGKGGSRAALYPHPQQLSREEKRRRRRATAKYRSAHATRERIRVEAFNLAFAELRK
                     LLPTLPPDKKLSKIEILRLAICYISYLNHVLDV"
     regulatory      2494..2499
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NHLH2"
                     /gene_synonym="bHLHa34; HEN2; HH27; NSCL2"
                     /note="hexamer: AATAAA"
     polyA_site      2512
                     /gene="NHLH2"
                     /gene_synonym="bHLHa34; HEN2; HH27; NSCL2"
                     /note="major polyA site"
ORIGIN      
        1 aattggtacc aggagagccc agaagccaca cacgcatctc tgcctctttg ctctggctct
       61 cccaccctct tcccgtcttt ctctgcttcc ttgtcactgt tactccagga gacgttcact
      121 tttcaccaac ctttctccaa gcatctccaa gccactgact atatatattt tgctacaaga
      181 gacctagaag aggaaaaaag gcacgagact tttcaacaca tcgtttaaaa aaatcatcaa
      241 cgaatttctt gcaatgtttg agaacaatta aaaggaaaaa gcgtttttta aaaaatctat
      301 caactaagtg aacaatcatt catatcgtct acatcctgag atattattgt ccctcgctgc
      361 ggacaccagc gagatgacag ctgctttttc atttttgaat gtaataaata tttgctgctt
      421 ttaatatttt ccggaatctc ccctcgctat tccttggaat tttaactcta aagattggag
      481 aacagattat caaaaaggct tttgcaagcc tccaaaatga tgctgagtcc ggaccaagca
      541 gcagattcgg accatcccag ctcggcgcac tcggatccgg agtccctggg cggcacggac
      601 accaaggtgc tcggcagcgt gtcggacctg gagccggtgg aggaggccga gggcgacggc
      661 aagggcggca gccgagccgc gctctacccg cacccgcagc agctgagccg cgaggagaag
      721 cgccgccgcc ggcgcgccac ggccaagtac cgctcggccc acgccacccg cgagcgcatc
      781 cgcgtggaag ccttcaactt ggccttcgcc gagctccgca aattgctgcc cacgctgccc
      841 ccggacaaga agctctccaa gatcgagatc ctgcgcctgg ccatctgcta catctcctat
      901 ctcaaccacg tcctggacgt gtagggcggg gtgcgccgcg gggggccgcc tgtcccggcg
      961 tccgcgaaac gctacggatc cggacgggcg ccgtcgctcg ggtggcggag gctgcggtgg
     1021 cccagcgaga cggccgcctc gagagacggc cggggaagaa gctcgctacc tgttctctct
     1081 ggtcagcagg gcgacgaggg aaggtttccg acgcaggcag gtggggttgt ctggcgagcc
     1141 cgggggctcg caggggggat tttccaggcc aggagaacct cgtggagaca cccgagatga
     1201 gccacttctg gggctcccca agggttgtgg ttttaaccca ctggagactt tgagttctcc
     1261 tacattcatc cgccacaaat cttaatgtgt tgaaagaatg agggcagaag ttcagagtat
     1321 gcaggctcat aactttaggc tatctggaat ttttctaatg gacaaatcac caaacactgg
     1381 gaaggaggag agaggaggga tctctcccat agagatggaa ggcacagaaa ggtgcgactg
     1441 gaaactttcc tttctgttgt gaaaataaag attatattag aatccaaata aaccctgaat
     1501 atttagtaag tttaaaaaga caaattgaga acaagtagac acactgtggg aggatctgag
     1561 cttggtgata ttttatcccc aagatatgac accaaggtag acaggaaaat ccatatttaa
     1621 atggaaactt taatatctga ttacttttgc aggcgaagtg cccctttata tatccaaaaa
     1681 catctatttg tgaccttaaa catgtggacc cataggtgca gttagaaaaa gacaacctat
     1741 ttttatttat gttagaagga gtagagtatt tttttcaaga catttatttt tcagagtggt
     1801 gatactttta ctttggatac tctgtgccaa tttatttata gtcaagtgtt tacacttttt
     1861 cctgtggaat aattatgtct aactttttac gtgtttgttg agattatact gtggtctttc
     1921 tttctgctct aattatattg cacttgtata acaaatttcc cacttctccc tgtttctaaa
     1981 catattttat atattaagat gtttgttctt gaaaggttct tttgttgtga gatcagcaac
     2041 actagcactt cactattata gttttttaaa aagtgtatta ttcttatctg tagttatgtc
     2101 tgagaagtcc tttacaagct gtttataagg agagtagctt ctttgtgtgt gtgatgtttg
     2161 tgcgtgtgat gaatttagca aattaagtta ttttcctaaa aaaaaaagaa aaaaagaatt
     2221 cagaactact ttcctctgtg acaccaaaaa gaaaagtcta taacctgaaa atgtttcatg
     2281 ttctctgctg tgaaactctt aaaacaagga gtgtatttta gagacaaggg aaaaaaacca
     2341 catctgctat ccaaagattt tagtcttttt cagggttttt ttgtgtctct gttgctttat
     2401 ataatgcaat attttgtagt gaaaatagat ataatctggt ttctatctga cgagtttttc
     2461 atatctcatg aatggtgcgc tgttttgcat ataaataaag gtatcaaata aa
//
